UL33_HCMVM
ID UL33_HCMVM Reviewed; 412 AA.
AC Q6SW98; D2K3K1;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=G-protein coupled receptor homolog UL33;
GN Name=UL33;
OS Human cytomegalovirus (strain Merlin) (HHV-5) (Human herpesvirus 5).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX NCBI_TaxID=295027;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15105547; DOI=10.1099/vir.0.79888-0;
RA Dolan A., Cunningham C., Hector R.D., Hassan-Walker A.F., Lee L.,
RA Addison C., Dargan D.J., McGeoch D.J., Gatherer D., Emery V.C.,
RA Griffiths P.D., Sinzger C., McSharry B.P., Wilkinson G.W.G., Davison A.J.;
RT "Genetic content of wild-type human cytomegalovirus.";
RL J. Gen. Virol. 85:1301-1312(2004).
RN [2]
RP REVIEW ON FUNCTION.
RX PubMed=16352349; DOI=10.1016/j.tips.2005.11.006;
RA Vischer H.F., Leurs R., Smit M.J.;
RT "HCMV-encoded G-protein-coupled receptors as constitutively active
RT modulators of cellular signaling networks.";
RL Trends Pharmacol. Sci. 27:56-63(2006).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=31519750; DOI=10.1074/jbc.ra119.007796;
RA van Senten J.R., Bebelman M.P., Fan T.S., Heukers R., Bergkamp N.D.,
RA van Gasselt P., Langemeijer E.V., Slinger E., Lagerweij T., Rahbar A.,
RA Stigter-van Walsum M., Maussang D., Leurs R., Musters R.J.P.,
RA van Dongen G.A.M.S., Soederberg-Naucler C., Wuerdinger T., Siderius M.,
RA Smit M.J.;
RT "The human cytomegalovirus-encoded G protein-coupled receptor UL33 exhibits
RT oncomodulatory properties.";
RL J. Biol. Chem. 294:16297-16308(2019).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32486172; DOI=10.3390/v12060594;
RA van Senten J.R., Bebelman M.P., van Gasselt P., Bergkamp N.D.,
RA van den Bor J., Siderius M., Smit M.J.;
RT "Human Cytomegalovirus-Encoded G Protein-Coupled Receptor UL33 Facilitates
RT Virus Dissemination via the Extracellular and Cell-to-Cell Route.";
RL Viruses 12:0-0(2020).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=33199520; DOI=10.1242/jcs.254268;
RA Krishna B.A., Wass A.B., Dooley A.L., O'Connor C.M.;
RT "CMV-encoded GPCR pUL33 activates CREB and facilitates its recruitment to
RT the MIE locus for efficient viral reactivation.";
RL J. Cell Sci. 134:0-0(2021).
CC -!- FUNCTION: G-protein-coupled receptor (vGPCR) that constitutively
CC activates multiple oncogenic signaling pathways including STAT3, AP-1,
CC phospholipase C, NF-kappa-B or cAMP-responsive element (CRE) pathways
CC (PubMed:31519750). Plays an important role in viral reactivation from
CC latency through activation of host CREB1, facilitating its recruitment
CC to the viral major immediate early (MIE) genes. In turn, expression of
CC the MIE-driven genes such as UL123 are de-repressed (PubMed:33199520).
CC Facilitates also virus dissemination via the extracellular and cell-to-
CC cell route (PubMed:32486172). {ECO:0000269|PubMed:31519750,
CC ECO:0000269|PubMed:32486172, ECO:0000269|PubMed:33199520}.
CC -!- SUBUNIT: Heterodimerizes with US28. {ECO:0000250|UniProtKB:P16849}.
CC -!- SUBCELLULAR LOCATION: Virion. Host cell membrane
CC {ECO:0000250|UniProtKB:P16849}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P16849}. Host cytoplasm
CC {ECO:0000269|PubMed:31519750}. Note=Present in the virion assembly
CC compartment (VAC) of HCMV-infected cells.
CC {ECO:0000269|PubMed:31519750}.
CC -!- DISRUPTION PHENOTYPE: UL33-deficient virus displays a growth defect due
CC to deficiency in extracellular transmission (PubMed:32486172). In
CC addition, UL33 disruption attenuates viral reactivation
CC (PubMed:33199520). {ECO:0000269|PubMed:32486172,
CC ECO:0000269|PubMed:33199520}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AY446894; AAR31598.1; -; Genomic_DNA.
DR RefSeq; YP_081492.1; NC_006273.2.
DR SMR; Q6SW98; -.
DR PRIDE; Q6SW98; -.
DR DNASU; 3077468; -.
DR GeneID; 3077468; -.
DR KEGG; vg:3077468; -.
DR Proteomes; UP000000938; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0039553; P:suppression by virus of host chemokine activity; IEA:UniProtKB-KW.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 3: Inferred from homology;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Host cell membrane; Host cytoplasm; Host membrane; Host-virus interaction;
KW Inhibition of host chemokines by virus; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix;
KW Viral immunoevasion; Virion.
FT CHAIN 1..412
FT /note="G-protein coupled receptor homolog UL33"
FT /id="PRO_0000416441"
FT TOPO_DOM 1..35
FT /note="Virion surface"
FT /evidence="ECO:0000255"
FT TRANSMEM 36..56
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..80
FT /note="Intravirion"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..101
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 102..106
FT /note="Virion surface"
FT /evidence="ECO:0000255"
FT TRANSMEM 107..127
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..147
FT /note="Intravirion"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 169..206
FT /note="Virion surface"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..227
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 228..244
FT /note="Intravirion"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..292
FT /note="Virion surface"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..313
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 314..412
FT /note="Intravirion"
FT /evidence="ECO:0000255"
FT REGION 377..412
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 7
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 23
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 105..188
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 412 AA; 46080 MW; 6ADD072CF5E5C928 CRC64;
MDTIIHNTTN RSTDTPHVNI TCNITEPLSA IRTTEAVINT FIIFVGGPLN AIVLITQLLT
NRVLGYSTPT IYMTNLYSTN FLTLTVLPFI VLSNQWLLPA SVASCKFLSV IYYSSCTVGF
ATVALIAADR YRVLHKRTYA RQSYRSTYII LLLTWFAGLI FSMPAAVYTT VVIHNGTNGQ
SSNGHATCVL YFIADEVYTV LLSWKVLLTL VWGAAPVIMM TWFYAFFYST VQRASQKQRS
RTLTFVSVLL ISFVALQTPY VSIMIFNSYA TAAWPMDCEH LTLRRTIGTL SRLVPHLHCL
INPILYALLG HDFLQRMRQC FRGQLLDRRA FLRSQQNQRA TAETNLAAGN NSQSVATSLD
TSSKNCNQHA KRSVSFNFPS GTWKGGQKTA SNDTSTKIPH RLSQSHHNLS GV
